The present invention relates to a pharmaceutical raw material containing magnetic particles, and more particularly, to a pharmaceutical raw material containing magnetic particles, which is used for preparing medicines or drugs for drug delivery system as a method for delivering drugs (hereinafter referred to merely as “DDS”), CT (computed tomography) diagnosis used in roentgen and MRI (magnetic resonance), and medical treatments such as thermotherapy in medical technology fields. More specifically, the present invention relates to a pharmaceutical raw material containing magnetic particles, which is capable of improving a delivery directivity of drugs containing magnetic particles to lesion tissues or cells, contrast sensitivity upon diagnosis using CT, exothermic property upon thermotherapy, etc.
In recent years, there have been studied drugs containing magnetic particles, which are used in the form of a composite material composed of magnetic iron oxide fine particles as a magnetic material, and a biocompatible substance such as a phospholipid, a protein and a water-soluble polymer (Japanese Patent Application Laid-open (KOKAI) Nos. 3-128331(1991), 4-52202(1992), 7-122410(1995) and 11-106391(1999) and Japanese Translation of International Patent Application Laid-open (KOHYO) No. 8-500700(1996)).
Also, in order to prepare a monodisperse aqueous solution of magnetic iron oxide fine particles, there are known a method of coating the surface of the respective particles with a surface-treating agent such as a surfactant (Japanese Patent Application Laid-open (KOKAI) No. 1-4002(1989)), a method of coating the surface of the respective particles with an inorganic material such as Al and Si (Japanese Patent Application Laid-open (KOKAI) No. 5-310429(1993)), a method of coating the surface of the respective particles with an organometallic polymer (Japanese Translation of International Patent Application Laid-open (KOHYO) No. 8-500700(1996)), etc.
Although these methods relate to techniques concerning magnetic particles-containing drugs using magnetic iron oxide particles, there are mainly described techniques for imparting a modifying function to the magnetic particles. Therefore, these methods may fail to sufficiently analyze the relation of characteristic factors between particle properties such as particle size or magnetic properties of the magnetic iron oxide fine particles and properties of the drugs containing magnetic particles.
In particular, it has been conventionally difficult to uniformly disperse and support the magnetic iron oxide fine particles on the biocompatible substance owing to magnetic coagulation inherent to the iron oxide particles. For this reason, hitherto, it has been required to use magnetic iron oxide particles having a large particle size.
In the case where such magnetic iron oxide particles having a large particle size are used for medical treatments, there is a high possibility that the iron oxide particles remain in vivo after the medical treatments, thereby failing to ensure a sufficient safety upon use thereof.
In consequence, it has been strongly required to develop a pharmaceutical material capable of not only exhibiting a uniform functionality, for example, a delivering capability for reagents, contrast sensitivity, exothermic property, etc., but also producing magnetic particles-containing drugs for diagnosis and medical treatments, which can exhibit a sufficient function, with a high reproducibility.
As described above, in order to produce such magnetic material-containing drugs having uniform characteristics with a high reproducibility, it is inevitably required to uniformly disperse and mix the biocompatible substance and the magnetic iron oxide fine particles with each other upon the drug-making process. For this purpose, it is also required that the magnetic iron oxide fine particles contained in the pharmaceutical raw material have a fine and uniform particle size, and the pharmaceutical raw material is in the form of a dispersed colloid aqueous solution containing the magnetic iron oxide fine particles.
However, when the magnetic iron oxide fine particles are dispersed in the solution using a surface-treating agent such as a surfactant, the surface-treating agent used tends to remain and be mixed in the resultant magnetic material-containing drugs, resulting in not only adverse influence on safety to living organisms, but also difficulty in mixing with the biocompatible substance. In addition, the removal of the surface-treating agent from the obtained drugs requires complicated procedures.
Under the circumstances of the above conventional problems, as a result of the present inventors' earnest study for solving the above problems, by noticing magnetic iron oxide fine particles as magnetic particles for drugs, it has been found that a monodisperse colloid aqueous solution of superparamagnetic iron oxide particles can exhibit a good dispersion stability under specific conditions. The present invention has been attained on the basis of the above finding.